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  • 1.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery: a potential new indication?2013In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 169, no 6, p. 885-889Article in journal (Refereed)
    Abstract [en]

    Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.

  • 2.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hypoglycemia in everyday life after gastric bypass and duodenal switch2015In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, no 1, p. 91-100Article in journal (Refereed)
    Abstract [en]

    Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

  • 3.
    Al-Shamkhi, Nasrin
    et al.
    Örebro Univ Hosp, Dept Internal Med, Örebro, Sweden.;Örebro Univ, Fac Med & Hlth, Sch Med Sci, Örebro, Sweden.;Uppsala Univ Hosp, Dept Endocrinol & Diabetol, Uppsala, Sweden.;Akadem Sjukhuset, Endokrin & Diabetesmottagningen, S-75185 Uppsala, Sweden..
    Berinder, Katarina
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Borg, Henrik
    Lund Univ, Skane Univ Hosp, Dept Endocrinol, Lund, Sweden..
    Burman, Pia
    Lund Univ, Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden..
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Hoybye, Charlotte
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Olsson, Daniel S.
    Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Gothenburg, Sweden.;AstraZeneca, BioPharmaceut R&D, Cardiovasc Renal & Metab CVRM, Gothenburg, Sweden..
    Ragnarsson, Oskar
    Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Gothenburg, Sweden.;Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden..
    Ekman, Bertil
    Linköping Univ, Dept Endocrinol Linköping & Norrköping, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish Pituitary Register2023In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 189, no 2, p. 217-224Article in journal (Refereed)
    Abstract [en]

    Objective: Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).

    Design and methods: Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.

    Results: Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm(3). Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.

    Conclusions: Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.

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  • 4.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farahmand, Bahman
    Ahlbom, Anders
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ljunghall, Sverker
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 47, p. 3624-3631Article in journal (Refereed)
    Abstract [en]

    AIMS:

    We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.

    METHODS AND RESULTS:

    All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.

    CONCLUSIONS:

    Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.

  • 5.
    Andersson, Kristofer
    et al.
    Karolinska Inst, Dept Dent Med, Div Pediat Dent, Huddinge, Sweden..
    Dahllöf, Goran
    Karolinska Inst, Dept Dent Med, Div Pediat Dent, Huddinge, Sweden.;Ctr Pediat Oral Hlth Res, Stockholm, Sweden..
    Lindahl, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Grigelioniene, Giedre
    Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Åström, Eva
    Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Pediat Neurol & Musculoskeletal Disorders & Home, Stockholm, Sweden..
    Malmgren, Barbro
    Karolinska Inst, Dept Dent Med, Div Pediat Dent, Huddinge, Sweden..
    Mutations in COL1A1 and COL1A2 and dental aberrations in children and adolescents with osteogenesis imperfecta - A retrospective cohort study2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176466Article in journal (Refereed)
    Abstract [en]

    Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, caused mainly by mutations in the collagen I genes (COL1A1 and COL1A2). Dentinogenesis imperfecta (DGI) and other dental aberrations are common features of OI. We investigated the association between collagen I mutations and DGI, taurodontism, and retention of permanent second molars in a retrospective cohort of 152 unrelated children and adolescents with OI. The clinical examination included radiographic evaluations. Teeth from 81 individuals were available for histopathological evaluation. COL1A1/2 mutations were found in 104 individuals by nucleotide sequencing. DGI was diagnosed clinically and radiographically in 29% of the individuals (44/152) and through isolated histological findings in another 19% (29/152). In the individuals with a COL1A1 mutation, 70% (7/10) of those with a glycine substitution located C-terminal of p. Gly305 exhibited DGI in both dentitions while no individual (0/7) with a mutation N-terminal of this point exhibited DGI in either dentition (p = 0.01). In the individuals with a COL1A2 mutation, 80% (8/10) of those with a glycine substitution located C terminal of p. Gly211 exhibited DGI in both dentitions while no individual (0/5) with a mutation N-terminal of this point (p = 0.007) exhibited DGI in either dentition. DGI was restricted to the deciduous dentition in 20 individuals. Seventeen had missense mutations where glycine to serine was the most prevalent substitution (53%). Taurodontism occurred in 18% and retention of permanent second molars in 31% of the adolescents. Dental aberrations are strongly associated with qualitatively changed collagen I. The varying expressivity of DGI is related to the location of the collagen I mutation. Genotype information may be helpful in identifying individuals with OI who have an increased risk of dental aberrations.

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  • 6.
    Arnardottir, Steinunn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Järås, Jacob
    Reg Canc Ctr RCC Stockholm Gotland, Stockholm, Sweden..
    Burman, Pia
    Lund Univ, Skanes Univ Hosp, Dept Endocrinol, Malmö, Sweden..
    Berinder, Katarina
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden..
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Erfurth, Eva Marie
    Lund Univ, Skanes Univ Hosp, Dept Endocrinol, Malmö, Sweden..
    Höybye, Charlotte
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden..
    Larsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Ragnarsson, Oskar
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden..
    Ekman, Bertil
    Linköping Univ, Dept Endocrinol Linköping, Dept Internal Med Norrköping, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Long-term outcomes of patients with acromegaly: a report from the Swedish Pituitary Register2022In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 186, no 3, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the treatment and long-term outcomes of patients with acromegaly from all healthcare regions in Sweden.

    Design and methods: Analysis of prospectively reported data from the Swedish Pituitary Register of 698 patients (51% females) with acromegaly diagnosed from 1991 to 2011. The latest clinical follow-up date was December 2012, while mortality data were collected for 28.5 years until June 2019.

    Results: The annual incidence was 3.7/million; 71% of patients had a macroadenoma, 18% had visual field defects, and 25% had at least one pituitary hormone deficiency. Eighty-two percent had pituitary surgery, 10% radiotherapy, and 39% medical treatment. At the 5- and 10-year follow-ups, insulin-like growth factor 1 levels were within the reference range in 69 and 78% of patients, respectively. In linear regression, the proportion of patients with biochemical control including adjuvant therapy at 10 years follow-up increased over time by 1.23% per year. The standardized mortality ratio (SMR) (95% CI) for all patients was 1.29 (1.11-1.49). For patients with biochemical control at the latest follow-up, SMR was not increased, neither among patients diagnosed between 1991 and 2000, SMR: 1.06 (0.85-1.33) nor between 2001 and2011, SMR: 0.87 (0.61-1.24). In contrast, non-controlled patients at the latest follow-up from both decades had elevated SMR, 1.90 (1.33-2.72) and 1.98 (1.24-3.14), respectively.

    Conclusions: The proportion of patients with biochemical control increased over time. Patients with biochemically controlled acromegaly have normal life expectancy, while non-controlled patients still have increased mortality. The high rate of macroadenomas and unchanged age at diagnosis illustrates the need for improvements in the management of patients with acromegaly.

  • 7.
    Banefelt, J.
    et al.
    Quantify Res, Stockholm, Sweden.
    Akesson, K. E.
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res, Malmo, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Spangeus, A.
    Linkoping Univ, Linkoping Univ Hosp, Linkoping, Sweden.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Karlsson, L.
    Quantify Res, Stockholm, Sweden.
    Strom, O.
    Quantify Res, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Ortsater, G.
    Quantify Res, Stockholm, Sweden.
    Libanati, C.
    UCB Biopharma Sprl, Allee Rech 60, B-1070 Brussels, Belgium.
    Toth, E.
    UCB Biopharma Sprl, Allee Rech 60, B-1070 Brussels, Belgium.
    Risk of imminent fracture following a previous fracture in a Swedish database study2019In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 30, no 3, p. 601-609Article in journal (Refereed)
    Abstract [en]

    The SummaryThis study examined the imminent risk of a future fracture within 1 and 2years following a first fracture in women aged 50years and older and assessed independent factors associated with risk of subsequent fractures. The study highlights the need to intervene rapidly after a fracture to prevent further fractures.IntroductionThis study aims to determine the imminent risk of subsequent fractures within 1 and 2years following a first fracture and to assess independent factors associated with subsequent fractures.MethodsRetrospective, observational cohort study of women aged 50years with a fragility fracture was identified from Swedish national registers. Clinical/demographic characteristics at the time of index fracture and cumulative fracture incidences up to 12 and 24months following index fracture were calculated. Risk factors for subsequent fracture were identified using multivariate regression analysis.ResultsTwo hundred forty-two thousand one hundred eight women (mean [SD] age 74 [12.5] years) were included. The cumulative subsequent fracture incidence at 12months was 7.1% (95% confidence interval [CI], 6.9-7.2) and at 24months was 12.0% (95% CI, 11.8-12.1). The rate of subsequent fractures was highest in the first month (similar to 15 fractures per 1000 patient-years) and remained steady between 4 and 24months (similar to 5 fractures/1000 patient-years). Higher age was an independent risk factor for imminent subsequent fractures (at 24months, sub-distribution hazard ratio [HR], 3.07; p<0.001 for women 80-89years [reference 50-59years]). Index vertebral fracture was a strong independent risk factor for subsequent fracture (sub-distribution HR, 2.72 versus hip fracture; p<0.001 over 12months; HR, 2.23; p<0.001 over 24months).ConclusionsOur findings highlight the need to intervene rapidly after any fragility fracture in postmenopausal women. The occurrence of a fragility fracture provides healthcare systems with a unique opportunity to intervene to reduce the increased risk of subsequent fractures.

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  • 8.
    Banefelt, J.
    et al.
    Quantify Res, Stockholm, Sweden..
    Akesson, K.
    Lund Univ, Dept Orthopaed, Skane Univ Hosp, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Spangeus, A.
    Linkoping Univ, Dept Endocrinol, Dept Med & Hlth Sci, Linkoping, Sweden..
    Karlsson, L.
    Quantify Res, Stockholm, Sweden..
    Strom, O.
    Quantify Res, Stockholm, Sweden.;Karolinska Inst, Dept Learning Informat Management & Eth, Stockholm, Sweden..
    Ortsater, G.
    Quantify Res, Stockholm, Sweden..
    Libanati, C.
    UCB Pharma, Brussels, Belgium..
    Toth, E.
    UCB Pharma, Brussels, Belgium..
    Short-Term Fracture (Fx) Incidence And Risk Factors Following Fracture In A Swedish Database Study2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S365-S365Article in journal (Other academic)
  • 9.
    Bengtsson, Daniel
    et al.
    Dept Internal Med, Halsogrand 2, S-39185 Kalmar, Sweden.;Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Ragnarsson, Oskar
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden..
    Berinder, Katarina
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Ekman, Bertil
    Linköping Univ, Dept Endocrinol Linköping, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Hoybye, Charlotte
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Burman, Pia
    Lund Univ, Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden..
    Wahlberg, Jeanette
    Linköping Univ, Dept Endocrinol Linköping, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Örebro Univ, Fac Med Sci, Örebro, Sweden..
    Psychotropic Drugs in Patients with Cushing's Disease Before Diagnosis and at Long-Term Follow-Up: A Nationwide Study2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 6, p. 1750-1760Article in journal (Refereed)
    Abstract [en]

    Context: Psychiatric symptoms are common in Cushing's disease (CD) and seem only partly reversible following treatment. Objective: To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up. Design: Nationwide longitudinal register-based study. Setting: University Hospitals in Sweden. Subjects: CD patients diagnosed between 1990 and 2018 (N = 372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis, and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed. Main outcome measures: Data from the Swedish Prescribed Drug Register and the Patient Register. Results: In the 5-year period before and at diagnosis, use of antidepressants (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.3-3.7]) and 2.3 [1.6-3.5]), anxiolytics [2.9 (1.6-5.3) and 3.9 (2.3-6.6)], and sleeping pills [2.1 (1.2-3.7) and 3.8 (2.4-5.9)] was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants [2.4 (1.53.9)] and sleeping pills [3.1 (1.9-5.3)]. Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (interquartile range 8.1-10.4) had higher use of antidepressants [OR 2.0 (1.1-3.8)] and sleeping pills [2.4 (1.3-4.7)], but not of drugs for hypertension. Conclusions: Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.

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  • 10.
    Bengtsson, Daniel
    et al.
    Dept Internal Med, Halsogrand 2, S-39185 Kalmar, Region Of Kalma, Sweden.;Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Ragnarsson, Oskar
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden..
    Berinder, Katarina
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Ekman, Bertil
    Linköping Univ, Dept Endocrinol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden..
    Hoybye, Charlotte
    Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Jaras, Jacob
    Reg Canc Ctr, Stockholm, Sweden..
    Valdemarsson, Stig
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Lund, Sweden..
    Burman, Pia
    Lund Univ, Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden..
    Wahlberg, Jeanette
    Linköping Univ, Dept Endocrinol, Linköping, Sweden.;Linköping Univ, Dept Hlth Med & Caring Sci, Linköping, Sweden.;Örebro Univ, Fac Med Sci, Örebro, Sweden..
    Increased Mortality Persists after Treatment of Cushing's Disease: A Matched Nationwide Cohort Study2022In: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 6, no 6Article in journal (Refereed)
    Abstract [en]

    Context: Whether biochemical remission normalizes life expectancy in Cushing's disease (CD) patients remains unclear. Previous studies evaluating mortality in CD are limited by using the expected number of deaths in the background population instead of the actual number in matched controls. Objective and setting: To study mortality by time-to-event analysis in an unselected nationwide CD patient cohort. Design and participants: Longitudinal data from the Swedish Pituitary Register of 371 patients diagnosed with CD from 1991 to 2018 and information from the Swedish Cause of Death Register were evaluated. Four controls per patient (n = 1484) matched at the diagnosis date by age, sex, and residential area were included. Main outcome measures: Mortality and causes of death. Results: The median diagnosis age was 44 years (interquartile range 32-56), and the median follow-up was 10.6 years (5.7-18.0). At the 1-, 5-, 10-, 15-, and 20-year follow-ups, the remission rates were 80%, 92%, 96%, 91%, and 97%, respectively. Overall mortality was increased in CD patients compared with matched controls [hazard ratio (HR) 2.1 (95% CI 1.5-2.8)1. The HRs were 1.5 (1.02-2.2) for patients in remission at the last follow-up In = 303), 1.7 (1.03-2.8) for those in remission after a single pituitary surgery In = 177), and 5.6 (2.7-11.6) for those not in remission (n = 31). Cardiovascular diseases (32/66) and infections (12/66) were overrepresented causes of death. Conclusions: Mortality was increased in CD patients despite biochemical remission compared to matched controls. The study highlights the importance of careful comorbidity monitoring, regardless of remission status.

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  • 11.
    Bjorvatn Saevik, Åse
    et al.
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway.
    Wolff, Anette B.
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway.
    Björnsdottir, Sigridur
    Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden.
    Simunkova, Katerina
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway.
    Schei Hynne, Martha
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway.
    Dolan, David William Peter
    Univ Bergen, Dept Informat, N-5020 Bergen, Norway.
    Bratland, Eirik
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med Genet, NO-5021 Bergen, Norway.
    Knappskog, Per M.
    Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med Genet, NO-5021 Bergen, Norway.
    Methlie, Paal
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway.
    Carlsen, Siri
    Stavanger Univ Hosp, Dept Endocrinol, N-4068 Stavanger, Norway.
    Isaksson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Bensing, Sophie
    Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden.
    Kämpe, Olle
    Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden; Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, S-17177 Stockholm, Sweden.
    Husebye, Eystein S.
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway; Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, S-17177 Stockholm, Sweden.
    Løvås, Kristian
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway.
    Øksnes, Marianne
    Univ Bergen, Dept Clin Sci, Lab Bldg, 8th Floor, Jonas Lies Vei 91B, N-5021 Bergen, Norway; Univ Bergen, KG Jebsen Ctr Autoimmune Disorders, NO-5021 Bergen, Norway; Karolinska Univ Hosp, Dept Endocrinol, S-17177 Stockholm, Sweden; Haukeland Hosp, Dept Med, NO-5021 Bergen, Norway.
    Potential Transcriptional Biomarkers to Guide Glucocorticoid Replacement in Autoimmune Addison's Disease2021In: Journal of the Endocrine Society, E-ISSN 2472-1972, Vol. 5, no 3, article id bvaa202Article in journal (Refereed)
    Abstract [en]

    Background

    No reliable biomarkers exist to guide glucocorticoid (GC) replacement treatment in autoimmune Addison’s disease (AAD), leading to overtreatment with alarming and persistent side effects or undertreatment, which could be fatal.

    Objective

    To explore changes in gene expression following different GC replacement doses as a means of identifying candidate transcriptional biomarkers to guide GC replacement in AAD.

    Methods

    Step 1: Global microarray expression analysis on RNA from whole blood before and after intravenous infusion of 100 mg hydrocortisone (HC) in 10 patients with AAD. In 3 of the most highly upregulated genes, we performed real-time PCR (rt-PCR) to compare gene expression levels before and 3, 4, and 6 hours after the HC infusion. Step 2: Rt-PCR to compare expression levels of 93 GC-regulated genes in normal versus very low morning cortisol levels in 27 patients with AAD.

    Results

    Step 1: Two hours after infusion of 100 mg HC, there was a marked increase in FKBP5, MMP9, and DSIPI expression levels. MMP9 and DSIPI expression levels correlated with serum cortisol. Step 2: Expression levels of CEBPB, DDIT4, FKBP5, DSIPI, and VDR were increased and levels of ADARB1, ARIDB5, and POU2F1 decreased in normal versus very low morning cortisol. Normal serum cortisol levels positively correlated with DSIPI, DDIT4, and FKBP5 expression.

    Conclusions

    We introduce gene expression as a novel approach to guide GC replacement in AAD. We suggest that gene expression of DSIPI, DDIT4, and FKBP5 are particularly promising candidate biomarkers of GC replacement, followed by MMP9, CEBPB, VDR, ADARB1, ARID5B, and POU2F1.

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  • 12.
    Björk, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Mellström, Dan
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.
    Karlsson, Magnus
    Lund Univ, Skane Univ Hosp, Dept Clin Sci & Orthoped Surg, Malmo, Sweden.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Haplotypes in the CYP2R1 gene are associated with levels of 25(OH)D and bone mineral density, but not with other markers of bone metabolism (MrOS Sweden)2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 12, article id e0209268Article in journal (Refereed)
    Abstract [en]

    Objective: Polymorphisms in the CYP2R1 gene encoding Vitamin D 25-hydroxylase have been reported to correlate with circulating levels of 25-OH vitamin D3 (25(OH)D). It is unknown whether these variations also affect overall bone metabolism. In order to elucidate the overall associations of polymorphisms in the CYP2R1, we studied haplotype tagging single nucleotide polymorphisms (SNPs) in the gene and serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23), as well as bone mineral density (BMD).

    Methods: Baseline data on serum parameters and BMD from MrOS Sweden, a prospective population-based cohort study of elderly men (mean age 75 years, range 69-81), were analyzed. Genotyping was performed for eight SNPs covering the CYP2R1 gene in 2868 men with available samples of DNA. Subjects were followed up concerning incidence of fracture during five years.

    Results: There was a significant genetic association with circulating levels of 25(OH)D (4.6-18.5% difference in mean values between SNP alleles), but there were no correlations with levels of calcium, phosphate, PTH or FGF23 for any genetic variant. No differences were found in fracture incidence between the variants. There was an inverse relationship between lower BMD and concomitant higher 25(OH)D for three of the haplotypes (p < 0.005).

    Conclusions: Common variants in the CYP2R1 gene encoding Vitamin D 25-hydroxylase correlate with levels of circulating 25(OH)D but do not otherwise associate with measures of calcium and phosphate homeostasis. Presence of the specific haplotypes may be an indicator of risk for low 25(OH)D levels, and may in addition be correlated to bone mineral density.

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  • 13.
    Björk, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Mellström, Dan
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg Sweden. Centre for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Ohlsson, Claes
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg Sweden. Centre for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Karlsson, Magnus
    Department of Clinical Sciences and Orthopedic Surgery, Lund University, Skåne University Hospital, Malmö..
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Polymorphisms in the CYP2R1 gene are associated with 25OHD3 and bone mineral density, but not with calcium and phosphate concentrations (MrOS Sweden).Manuscript (preprint) (Other academic)
  • 14.
    Björk, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ribom, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Scragg, R.
    Univ Auckland, Sch Populat Hlth, Sect Epidemiol & Biostat, Auckland, New Zealand.
    Mellstrom, D.
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin, Geriatr Med,Nutr, Gothenburg, Sweden.
    Grundberg, E.
    McGill Univ, Dept Human Genet, Montreal, PQ, Canada;McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
    Ohlsson, C.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.
    Karlsson, M.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci & Orthoped Surg, Malmo, Sweden.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Variations in the vitamin D receptor gene are not associated with measures of muscle strength, physical performance, or falls in elderly men: Data from MrOS Sweden2019In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 187, p. 160-165Article in journal (Refereed)
    Abstract [en]

    The vitamin D receptor (VDR) has been proposed as a candidate gene for several musculoskeletal phenotypes. However, previous results on the associations between genetic variants of the VDR with muscle strength and falls have been contradictory. The MrOS Sweden survey, a prospective population-based cohort study of 3014 elderly men (mean age 75 years, range 69-81) offered the opportunity to further investigate these associations. At baseline, data were collected on muscle strength and also the prevalence of falls during the previous 12 months. Genetic association analysis was performed for 7 Single Nucleotide Polymorphisms (SNPs), covering the genetic region surrounding the VDR gene in 2924 men with available samples of DNA. Genetic variations in the VDR were not associated with five different measurements of muscle strength or physical performance (hand grip strength right and left, 6 m walking test (easy and narrow) and timed-stands test). However, one of the 7 SNPs of the gene for the VDR receptor, rs7136534, was associated with prevalence of falls (33.6% of the AA, 14.6% of the AG and 16.5% of the GG allele). In conclusion, VDR genetic variants are not related to muscle strength or physical performance in elderly Swedish men. The role of the rs7136534 SNP for the occurrence of falls is not clear.

  • 15.
    Björk, Anne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ribom, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Scragg, Robert
    Section of Epidemiology & Biostatistics, School of Population Health, University of Auckland, Auckland, New Zeeland.
    Mellström, Dan
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg Sweden. Centre for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Grundberg, Elin
    Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, McGill University, Montreal, Quebec, Canada.
    Ohlsson, Claes
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg Sweden. Centre for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Karlsson, Magnus
    Department of Clinical Sciences and Orthopedic Surgery, Lund University, Skåne University Hospital, Malmö..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Genetic variation in the vitamin D receptor gene is not associated with measures of muscle strength, physical performance, or falls in elderly men. Data from MrOS Sweden.Manuscript (preprint) (Other academic)
  • 16. Bolinder, J.
    et al.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Johansson, L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilding, J.
    Langkilde, A. M.
    Sjöstrom, C. D.
    Sugg, J.
    Parikh, S.
    Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin2014In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 16, no 2, p. 159-169Article in journal (Refereed)
    Abstract [en]

    Aims

    Dapagliflozin, a highly selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycaemia and weight in patients with type2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. Long-term glycaemic control, body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment.

    Methods

    This randomized, double-blind, placebo-controlled study (NCT00855166) enrolled patients with T2DM [mean: age 60.7 years; HbA1c 7.2%; body mass index (BMI) 31.9 kg/m(2); body weight 91.5 kg] inadequately controlled on metformin. Patients (N=182) were randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 102, changes from baseline in HbA1c, weight, waist circumference, total body fat mass as measured by dual-energy X-ray absorptiometry (DXA), serum markers of bone turnover, bone mineral density (BMD) as measured by DXA, and adverse events were evaluated.

    Results

    A total of 140 patients (76.9%) completed the study. Over 102 weeks, dapagliflozin-treated patients showed reductions in HbA1c by -0.3%, weight by -4.54 kg, waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia. Compared with placebo, no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks. One fracture occurred in each treatment group. The frequency of urinary tract infection (UTI) and genital infection was similar in both treatment groups.

    Conclusions

    Over 102 weeks, dapagliflozin improved glycaemic control, and reduced weight and fat mass, without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin.

  • 17.
    Borgström, F.
    et al.
    Quantify Res, Stockholm, Sweden..
    Olafsson, G.
    Quantify Res, Stockholm, Sweden..
    Jonsson, E.
    Quantify Res, Stockholm, Sweden..
    Ström, O.
    Quantify Res, Stockholm, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Akesson, K.
    Skane Univ Hosp, Dept Orthoped, Lund, Sweden.;Lund Univ, Clin Sci Malmo, Lund, Sweden..
    Spangeus, A.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Kanis, J. A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    A Simulation Model For The Treatment Pathway Of Osteoporosis2016In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, p. S60-S60Article in journal (Other academic)
  • 18.
    Burman, Pia
    et al.
    Lund Univ, Skane Univ Hosp Malmo, Dept Endocrinol, S-20502 Malmo, Sweden..
    Edén-Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ekman, Bertil
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Schwarcz, Erik
    Univ Orebro, Fac Med & Hlth, Dept Internal Med, SE-70182 Orebro, Sweden..
    Wahlberg, Jeanette
    Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Limited value of cabergoline in Cushing's disease: a prospective study of a 6-week treatment in 20 patients2016In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 174, no 1, p. 17-24Article in journal (Refereed)
    Abstract [en]

    Context and objective: The role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after >= 1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD. Design: Twenty patients (19 naive and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks. Methods: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end. Results: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study. Conclusions: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

  • 19.
    Bäcklund, Nils
    et al.
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.
    Brattsand, Göran
    Umeå Univ, Dept Med Biosci, Clin Chem, Umeå, Sweden.
    Israelsson, Marlen
    Umeå Univ, Dept Med Biosci, Clin Chem, Umeå, Sweden.
    Ragnarsson, Oskar
    Univ Gothenburg, Inst Med, Dept Internal Med & Clin Nutr, Sahlgrenska Acad, Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.
    Burman, Pia
    Lund Univ, Skåne Univ Hosp, Dept Endocrinol, Malmö, Sweden.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Høybye, Charlotte
    Karolinska Inst, Patient Area Endocrinol & Nephrol Inflammat & Inf, Dept Mol Med & Surg, Stockholm, Sweden; Karolinska Univ Hosp, Stockholm, Sweden.
    Berinder, Katarina
    Karolinska Inst, Patient Area Endocrinol & Nephrol Inflammat & Inf, Dept Mol Med & Surg, Stockholm, Sweden; Karolinska Univ Hosp, Stockholm, Sweden.
    Wahlberg, Jeanette
    Linköping Univ, Dept Med & Hlth Sci, Dept Endocrinol, Linköping, Sweden.
    Olsson, Tommy
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.
    Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome2020In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 182, no 6, p. 569-582Article in journal (Refereed)
    Abstract [en]

    Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).

    Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08: 00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves.

    Results: The upper reference limits of salivary cortisol and cortisone at 23: 00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected wit h a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h.

    Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.

  • 20.
    Bäcklund, Nils
    et al.
    Umeå Univ, Dept Publ Hlth & Clin Med, S-90187 Umeå, Sweden..
    Brattsand, Göran
    Umeå Univ, Dept Med Biosci, Umeå, Sweden..
    Lundstedt, Staffan
    Umeå Univ, Dept Med Biosci, Umeå, Sweden..
    Aardal, Elisabeth
    Linköping Univ, Dept Clin Chem, Linköping, Sweden.;Linköping Univ, Dept Biomed & Clin Sci, Linköping, Sweden..
    Bartuseviciene, Inga
    Karolinska Univ Hosp, Dept Clin Chem, Stockholm, Sweden..
    Berinder, Katarina
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden..
    Höybye, Charlotte
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol, Stockholm, Sweden..
    Burman, Pia
    Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden..
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Isaksson, Anders
    Lund Univ, Dept Clin Chem & Pharmacol, Lund, Sweden..
    Blomgren, Anders
    Lund Univ, Dept Clin Chem & Pharmacol, Lund, Sweden..
    Ragnarsson, Oskar
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.;Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden..
    Rüetschi, Ulrika
    Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden..
    Wahlberg, Jeanette
    Örebro Univ, Fac Med & Hlth, Sch Med Sci, Örebro, Sweden.;Örebro Univ Hosp, Dept Med, Örebro, Sweden..
    Olsson, Tommy
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods2023In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 61, no 10, p. 1780-1791Article in journal (Refereed)
    Abstract [en]

    Objectives: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS.Methods: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves.Results: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs =0.96.Conclusions: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.

  • 21.
    Calissendorff, Jan
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden..
    Cramon, Per Karkov
    Rigshospitalet, Copenhagen Univ Hosp, Dept Clin Physiol & Nucl Med, Copenhagen, Denmark..
    Hallengren, Bengt
    Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden.;Lund Univ, Dept Clin Sci, Lund, Sweden..
    Khamisi, Selwan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Dept Endocrinol & Diabet, Uppsala, Sweden..
    Lantz, Mikael
    Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden.;Lund Univ, Dept Clin Sci, Lund, Sweden..
    Planck, Tereza
    Skane Univ Hosp, Dept Endocrinol, Malmö, Sweden.;Lund Univ, Dept Clin Sci, Lund, Sweden..
    Sjölin, Gabriel
    Örebro Univ Hosp, Fac Med & Hlth, Örebro, Sweden..
    Wallin, Göran
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Örebro Univ Hosp, Fac Med & Hlth, Örebro, Sweden..
    Holmberg, Mats
    Karolinska Univ Hosp, ANOVA, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Inst, Dept Med, SE-17676 Stockholm, Sweden..
    Long-Term Outcome of Graves' Disease: A Gender Perspective2023In: Women's Health Reports, E-ISSN 2688-4844, Vol. 4, no 1, p. 487-496Article in journal (Refereed)
    Abstract [en]

    Introduction: In gender-skewed conditions such as Graves' disease (GD), the outcome naturally becomes dominated by the majority. This may lead to gender-biased misunderstandings regarding treatment outcomes. This especially holds true when complications, such as depression, are unevenly distributed. We have, therefore, studied the long-term outcome of GD from a gender perspective.Materials and Methods: A cohort of 1186 patients with GD was included in a follow-up 6-10 years after inclusion. Choice of treatment, the feeling of recovery, long-term treatment, comorbidity, and quality of life were investigated with questionnaires. All results were studied sex-divided.Results: We included 973 women and 213 men. There was no difference between men and women in the choice of treatment. At follow-up, women scored significantly worse in the general questionnaire 36-item Short-Form Health Status (SF-36) domain bodily pain and in the thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) domains depression, impaired sex life, and cosmetic complaints, all p < 0.05. Women were twice as likely (29.5%) to be treated with levothyroxine after successful treatment with antithyroid drugs (ATD) compared with men (14.9%, p < 0.05).Conclusion: After treatment for GD, women were more affected by depression, impaired sex life, cosmetic issues, and bodily pain despite successful cure of hyperthyroidism. The prevalence of hypothyroidism was also doubled in women. Whether these observed gender differences reflect a worse outcome of GD in women or a natural consequence of a higher prevalence of these symptoms and autoimmunity in the female population is difficult to disentangle. Nevertheless, several years after GD, women reveal more persistent symptoms.

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  • 22.
    Carlzon, Daniel
    et al.
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Svensson, Johan
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Petzold, Max
    Univ Gothenburg, Sahlgrenska Acad, Ctr Appl Biostat, Gothenburg, Sweden..
    Karlsson, Magnus K.
    Lund Univ, Skane Univ Hosp, Dept Orthopaed & Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Haghsheno, Mohammad-Ali
    Univ Gothenburg, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Damber, Jan-Erik
    Univ Gothenburg, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Mellström, Dan
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Ohlsson, Claes
    Univ Gothenburg, Inst Med, Sahlgrenska Acad CBAR, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Insulin-like growth factor I and risk of incident cancer in elderly men - results from MrOS (Osteoporotic Fractures in Men) in Sweden2016In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 84, no 5, p. 764-770Article in journal (Refereed)
    Abstract [en]

    ObjectiveStudies of the association between circulating IGF-I and cancer risk have shown conflicting results. We have previously observed a U-shaped association between IGF-I and cancer mortality. This study test the hypotheses of a U-shaped association between IGF-I and incident cancer. DesignElderly men (2368), randomly recruited from the general community. MethodsIGF-I was measured in a cohort of elderly men. Complete data for incident cancer were obtained from the Swedish Cancer Registry. Statistical analyses included Cox proportional hazards regressions with or without a spline approach. ResultsThree hundred and sixty-nine participants had incident cancer after baseline. Prostate cancer was most frequent (n = 140). There was no association between serum IGF-I and all cancer or prostate cancer incidence. However, there was a nonlinear association between IGF-I and nonprostate cancer incidence (P = <005). Exploratory analyses were performed for low and high serum IGF-I (quintiles 1 and 5) vs intermediate (quintiles 2-4, referent). There was a tendency of increased nonprostate cancer risk in men with high IGF-I (HR = 126, 95% confidence interval (CI): 092-171, P = 015). After excluding participants with follow-up of less than 26 years (half median follow-up time), to control for potential diagnostic delay, the association was statistically significant (HR = 155, CI: 103-235). ConclusionThere was a significant nonlinear association between IGF-I and nonprostate cancer. No association between IGF-I and prostate cancer was observed. Future studies are warranted to further investigate this nonlinear association, including whether IGF-I concentration is a reproducible, and useful, risk marker of nonprostate cancer.

  • 23. Carlzon, Daniel
    et al.
    Svensson, Johan
    Petzold, Max
    Karlsson, Magnus K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Tivesten, Asa
    Mellstrom, Dan
    Ohlsson, Claes
    Both Low and High Serum IGF-1 Levels Associate With Increased Risk of Cardiovascular Events in Elderly Men2014In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, no 11, p. E2308-E2316Article in journal (Refereed)
    Abstract [en]

    Context: Most previous prospective studies suggest that low serum IGF-1 associates with increased risk of cardiovascular disease (CVD) events whereas other studies suggest that high serum IGF-1 associates with increased risk of CVD events. Objective: We tested the hypothesis that not only low, but also high serum IGF-1 levels associate with increased risk of CVD events in elderly men. Setting and Design: Serum IGF-1 levels were measured in 2901 elderly men (age 69-81 years) included in the Swedish cohort of the prospective, population-based Osteoporotic Fractures in Men Study (MrOS), Sweden cohort. Data for CVD events were obtained from national Swedish registers with no loss of followup. Results: During followup (median, 5.1 y) 589 participants experienced a CVD event. The association between serum IGF-1 and risk of CVD events was nonlinear, and restricted cubic spline Cox regression analysis revealed a U-shaped association between serum IGF-1 levels and CVD events (P < .01 for nonlinearity). Low as well as high serum IGF-1 (quintile 1 or 5 vs quintiles 2-4) significantly associated with increased risk for CVD events (hazard ratio [HR] = 1.25, 95% confidence interval, [CI], 1.02-1.54; and HR = 1.35, 95% CI 1.10-1.66, respectively). These associations remained after adjustment for prevalent CVD and multiple risk factors. High serum IGF-1 associated with increased risk of coronary heart disease (CHD) events but not with risk of cerebrovascular events. Conclusions: Both low and high serum IGF-1 levels are risk markers for CVD events in elderly men. The association between high serum IGF-1 and CVD events is mainly driven by CHD events.

  • 24.
    Casar Borota, Olivera
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Boldt, Henning Bünsow
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Andersen, Marianne Skovsager
    Baussart, Bertrand
    Bengtsson, Daniel
    Berinder, Katarina
    Ekman, Bertil
    Feldt-Rasmussen, Ulla
    Höybye, Charlotte
    Jørgensen, Jens Otto L
    Kolnes, Anders Jensen
    Korbonits, Márta
    Rasmussen, Åse Krogh
    Lindsay, John R
    Loughrey, Paul Benjamin
    Maiter, Dominique
    Manojlovic-Gacic, Emilija
    Pahnke, Jens
    Poliani, Pietro Luigi
    Popovic, Vera
    Ragnarsson, Oskar
    Schalin-Jäntti, Camilla
    Scheie, David
    Tóth, Miklós
    Villa, Chiara
    Wirenfeldt, Martin
    Kunicki, Jacek
    Burman, Pia
    Corticotroph aggressive pituitary tumors and carcinomas frequently harbour ATRX mutations2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 4, p. 1183-1194Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Aggressive pituitary tumours (APTs) are characterised by unusually rapid growth and lack of response to standard treatment. About 1-2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumours are overrepresented amongst APTs and PCs. Mutations in the ATRX gene, regulating chromatin remodelling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumours.

    OBJECTIVE: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs.

    DESIGN: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumours lacking ATRX immunolabeling, mutational status of the ATRX gene was explored.

    RESULTS: Nine of the 48 tumours (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18 - 28%) than in those with APTs (4/30 - 13%). Lack of ATRX was most common in the corticotroph tumours, 7/22 (32%), vs 2/24 (8%) in the tumours of the Pit-1 lineage. Loss-of-function ATRX mutations were found in all the nine ATRX immuno-negative cases: nonsense mutations (n=4), frameshift deletions (n=4) and large deletions affecting 22-28 of the 36 exons (n=3). More than one ATRX gene defect was identified in two PCs.

    CONCLUSION: ATRX mutations occur in a subset of aggressive pituitary tumours and are more common in corticotroph tumours. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumours.

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  • 25.
    Cawthon, Peggy M.
    et al.
    Calif Pacific Med Ctr Res Inst, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA..
    Patel, Sheena M.
    Calif Pacific Med Ctr Res Inst, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA..
    Kritchevsky, Stephen B.
    Wake Forest Sch Med, Sticht Ctr Hlth Aging & Alzheimers Prevent, Winston Salem, NC 27101 USA..
    Newman, Anne B.
    Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA..
    Santanasto, Adam
    Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA..
    Kiel, Douglas P.
    Beth Israel Deaconess Med Ctr, Dept Med, Hebrew SeniorLife, Marcus Inst Aging Res, Boston, MA 02215 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Travison, Thomas G.
    Beth Israel Deaconess Med Ctr, Dept Med, Hebrew SeniorLife, Marcus Inst Aging Res, Boston, MA 02215 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Lane, Nancy
    Univ Calif Davis, Med Ctr, Ctr Musculoskeletal Hlth, Sacramento, CA 95817 USA.;Univ Calif Davis, Med Ctr, Dept Internal Med, Sacramento, CA 95817 USA..
    Cummings, Steven R.
    Calif Pacific Med Ctr Res Inst, 550 16th St,2nd Floor,Box 0560, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA..
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland, OR 97201 USA..
    Duchowny, Kate A.
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA..
    Kwok, Timothy
    Chinese Univ Hong Kong, Fac Med, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Fac Med, Sch Publ Hlth, Shatin, Hong Kong, Peoples R China..
    Hirani, Vasant
    Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia..
    Schousboe, John
    HealthPartners Inst, Bloomington, MN USA.;Univ Minnesota, Div Hlth Policy & Management, Minneapolis, MN USA..
    Karlsson, Magnus K.
    Lund Univ, Skane Univ Hosp, Dept Orthoped & Clin Sci Malmö, Clin & Mol Osteoporosis Res Unit, Lund, Sweden..
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med,Dept Internal Med & Clin Nutr, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Drug Treatment, Reg Vastra Gotaland, Gothenburg, Sweden..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med,Dept Internal Med & Clin Nutr, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Drug Treatment, Reg Vastra Gotaland, Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Xue, Qian-Li
    Johns Hopkins Med Inst, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.;Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA..
    Shardell, Michelle
    Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA..
    Jordan, Joanne M.
    Univ N Carolina, Thurston Arthrit Res Ctr, Sch Med, Chapel Hill, NC 27515 USA..
    Pencina, Karol M.
    Beth Israel Deaconess Med Ctr, Dept Med, Hebrew SeniorLife, Marcus Inst Aging Res, Boston, MA 02215 USA.;Harvard Med Sch, Boston, MA 02115 USA..
    Fielding, Roger A.
    Tufts Univ, Jean Mayer US Dept Agr Human Nutr, Nutr Exercise Physiol & Sarcopenia Lab, Res Ctr Aging, Boston, MA 02111 USA..
    Magaziner, Jay
    Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA..
    Correa-de-Araujo, Rosaly
    NIA, Bethesda, MD 20892 USA..
    Bhasin, Shalender
    Harvard Med Sch, Brigham & Womens Hosp, Boston Claude D Pepper Older Amer Independence Ct, Boston, MA 02115 USA..
    Manini, Todd M.
    Univ Florida, Gainesville, FL USA..
    What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without?: A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium2021In: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 76, no 10, p. E321-E327Article in journal (Refereed)
    Abstract [en]

    Background: Cut-points to define slow walking speed have largely been derived from expert opinion. Methods: Study participants (13 589 men and 5043 women aged >= 65years) had walking speed (m/s) measured over 4-6 m (mean +/- SD: 1.20 +/- 0.27 m/s in men and 0.94 +/- 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not. Results: Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed >= 0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed >= 0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed >= 1.00m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed >= 0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed >= 0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants. Conclusions: Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.

  • 26.
    Clewemar, Pantelis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hailer, Yasmin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Klar, Joakim
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Stattin, Eva-Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Expanding the phenotypic spectrum of osteogenesis imperfecta type V including heterotopic ossification of muscle origins and attachments2019In: Molecular Genetics & Genomic Medicine, ISSN 2324-9269, Vol. 7, no 7, article id e00723Article in journal (Refereed)
    Abstract [en]

    Background

    Osteogenesis imperfecta (OI) is a clinical and genetic heterogeneous group of connective tissue disorders, characterized by bone fragility and a propensity to fracture.

    Methods

    In this report we describe the clinical phenotype of two patients, a 28‐year‐old woman and her mother (54 years old), both with a history of short stature and multiple fractures.

    Results

    Exome sequencing revealed the recurring IFITM5:c.‐14 C>T variant causing OI type V. Both patients had several fractures during childhood. CT‐scan and scintigraphy showed ossification of the origin and attachment of muscles and hypertrophic callus formation.

    Conclusion

    Ossification of the origin and attachment of muscles seems to be part of the phenotype in patients with OI type V.

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  • 27.
    Cunningham, Janet L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Neuroradiologi.
    Cervenka, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Gallwitz, Maike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry.
    Säll, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Psychiatry. Psychiatry, Uppsala University Hospital, Uppsala, Sweden.
    Schmidt, Peter T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Rönnelid, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Persson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Burman, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Neurology.
    Experiences in implementing immunopsychiatry in real life2023In: Journal of Affective Disorders Reports, E-ISSN 2666-9153, Vol. 13, article id 100597Article in journal (Refereed)
    Abstract [en]

    Immunological mechanisms, both alone and in combination, are associated with a broad range of psychiatric disorders encompassing autoimmune, autoinflammatory disorders but also genetic, metabolic, or other immunological disorders. Early treatment improves the outcome for autoimmune disorders, but early diagnosis is more difficult when isolated psychiatric symptoms are manifestations of autoimmunity. Treatment of these cases must encompass integrated models of disease, as both systemic autoimmunity and psychological processes influence mental health. Several challenges need to be overcome to efficiently merge psychiatric and somatic disease paradigms and medical care ranging from language and conceptual barriers to organizational barriers. Since 2015, the Immunopsychiatry team at Uppsala University has developed a collaborative multidisciplinary approach to improve and integrate care for patients with moderate to severe psychiatric disorders. Based on this experience, we have outlined the obstacles to be overcome in taking steps forward to achieve the long-term goal of understanding and early detection and identification of treatable immunological conditions within the psychiatric patient population; the described framework of evaluations and work-flow may serve as a model for other centers.

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    Experiences in implementing immunopsychiatry in real life
  • 28. Ellegaard, Maria
    et al.
    Karlsson, Magnus
    Lorentzon, Mattias
    Ohlsson, Claes
    Mellstrom, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Schwarz, Peter
    Jorgensen, Niklas Rye
    Single-nucleotide polymorphism in the P2Y(2) receptor gene is associated with bone mineral density in a cohort of Swedish elderly men2014In: Purinergic Signalling Purinergic Signalling, ISSN 1573-9538, E-ISSN 1573-9546, Vol. 10, no 4, p. 751-751, article id B015Article in journal (Other academic)
  • 29.
    Eriksson, Anna L.
    et al.
    Univ Gothenburg, Sahlgrenska Osteoporosis Ctr, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr,Inst Med, SE-41345 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Clin Pharmacol, Reg Vastra Gotaland, SE-41345 Gothenburg, Sweden..
    Friedrich, Nele
    Univ Med Greifswald, Inst Clin Chem & Lab Med, DE-17489 Greifswald, Germany..
    Karlsson, Magnus K.
    Lund Univ, Skane Univ Hosp, Dept Orthopaed & Clin Sci, SE-21774 Malmö, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Osteoporosis Ctr, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr,Inst Med, SE-41345 Gothenburg, Sweden.;Univ Gothenburg, Geriatr Med, Inst Med, Dept Internal Med & Clin Nutr, S-43180 Mölndal, Sweden.;Sahlgrens Univ Hosp, Geriatr Med, S-43180 Mölndal, Sweden.;Australian Catholic Univ, Mary McKillop Inst Hlth Res, Melbourne, Vic, Australia..
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Osteoporosis Ctr, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr,Inst Med, SE-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, SE-41345 Gothenburg, Sweden..
    Wallaschofski, Henri
    Univ Med Greifswald, Inst Clin Chem & Lab Med, DE-17489 Greifswald, Germany..
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Osteoporosis Ctr, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr,Inst Med, SE-41345 Gothenburg, Sweden.;Univ Gothenburg, Geriatr Med, Inst Med, Dept Internal Med & Clin Nutr, S-43180 Mölndal, Sweden.;Sahlgrens Univ Hosp, Geriatr Med, S-43180 Mölndal, Sweden..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Osteoporosis Ctr, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr,Inst Med, SE-41345 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Clin Pharmacol, Reg Vastra Gotaland, SE-41345 Gothenburg, Sweden..
    Serum Glycine Levels Are Associated With Cortical Bone Properties and Fracture Risk in Men2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 12, p. E5021-E5029Article in journal (Refereed)
    Abstract [en]

    Context: In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD). Objective: To investigate associations for serum and urinary glycine levels with BMD, bone microstructure, and fracture risk in men. Methods: In the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n = 965) and 5-year follow-up (n = 546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high-resolution peripheral quantitative computed tomography. Urinary (n = 2682) glycine was analyzed at baseline. X-ray-validated fractures (n = 594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures). Results: Circulating glycine levels were inversely associated with femoral neck (FN)BMD. A meta-analysis (n = 7543) combining MrOS Sweden data with data from 3 other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (P = 7.7 x 10-9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (P = 0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum: hazard ratio [HR] per SD increase = 1.22, 95% CI, 1.05-1.43; urine: HR = 1.13, 95% CI, 1.02-1.24). These fracture associations were only marginally reduced in models adjusted by FRAX with BMD. Conclusions: Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.

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  • 30. Eriksson, Anna L.
    et al.
    Movérare-Skrtic, Sofia
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Karlsson, Magnus
    Mellström, Dan
    Ohlsson, Claes
    High-Sensitivity CRP Is an Independent Risk Factor for All Fractures and Vertebral Fractures in Elderly Men: The MrOS Sweden Study2014In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, no 2, p. 418-423Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies have shown low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) to be associated with fracture risk in women. However, it is still unclear whether hs-CRP is also associated with fracture risk in men. We therefore measured serum levels of hs-CRP in 2910 men, mean age 75 years, included in the prospective population-based MrOS Sweden cohort. Study participants were divided into tertile groups based on hs-CRP level. Fractures occurring after the baseline visit were validated (average follow-up 5.4 years). The incidence for having at least one fracture after baseline was 23.9 per 1000 person-years. In Cox proportional hazard regression analyses adjusted for age, hs-CRP was related to fracture risk. The hazard ratio (HR) of fracture for the highest tertile of hs-CRP, compared with the lowest and the medium tertiles combined, was 1.48 (95% CI, 1.20-1.82). Multivariate adjustment for other risk factors for fractures had no major effect on the associations between hs-CRP and fracture. Results were essentially unchanged after exclusion of subjects with hs-CRP levels greater than 7.5mg/L, as well as after exclusion of subjects with a first fracture within 3 years of follow-up, supporting that the associations between hs-CRP and fracture risk were not merely a reflection of a poor health status at the time of serum sampling. Femoral neck bone mineral density (BMD) was not associated with hs-CRP, and the predictive role of hs-CRP for fracture risk was essentially unchanged when femoral neck BMD was added to the model (HR, 1.37; 95% CI, 1.09-1.72). Exploratory subanalyses of fracture type demonstrated that hs-CRP was clearly associated with clinical vertebral fractures (HR, 1.61; 95% CI, 1.12-2.29). We demonstrate, using a large prospective population-based study, that elderly men with high hs-CRP have increased risk of fractures, and that these fractures are mainly vertebral. The association between hs-CRP and fractures was independent of BMD. (c) 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  • 31.
    Espiard, Stephanie
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden..
    McQueen, Johanna
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden..
    Sherlock, Mark
    Beaumont Hosp, Dept Endocrinol, Dublin 9, Co Dublin, Ireland.;Royal Coll Surgeons Ireland, Dublin 9, Co Dublin, Ireland..
    Ragnarsson, Oskar
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden..
    Bergthorsdottir, Ragnhildur
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden..
    Burman, Pia
    Skane Univ Hosp Malmö, Dept Endocrinol, S-21428 Malmö, Sweden.;Lund Univ, S-22100 Lund, Sweden..
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, S-90187 Umeå, Sweden..
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Engstrom, Britt Eden
    Uppsala Univ Hosp, Dept Med Sci Endocrinol & Metab, S-75237 Uppsala, Sweden..
    Skrtic, Stanko
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden.;AstraZeneca R&D, S-43150 Mölndal, Sweden..
    Wahlberg, Jeanette
    Linköping Univ, Dept Endocrinol, Dept Med & Hlth Sci, Dept Clin & Expt Med, S-58183 Linköping, Sweden..
    Stewart, Paul M.
    Univ Leeds, Fac Med & Hlth, Leeds LS2 9JT, W Yorkshire, England..
    Johannsson, Gudmundur
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Endocrinol, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, S-41345 Gothenburg, Sweden..
    Improved Urinary Cortisol Metabolome in Addison Disease: A Prospective Trial of Dual-Release Hydrocortisone2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 3, p. 814-825Article in journal (Refereed)
    Abstract [en]

    Context: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism. Objective: This work aimed to study cortisol metabolism during DR-HC and TID-HC. Design: A randomized, 12-week, crossover study was conducted. Intervention and Participants: DC-HC and same daily dose of TID-HC were administered to patients with primary adrenal insufficiency (n=50) vs healthy individuals (n=124) as controls. Main Outcome Measures: Urinary corticosteroid metabolites were measured by gas chromatography/mass spectrometry at 24-hour urinary collections. Results: Total cortisol metabolites decreased during DR-HC compared to TID-HC (P<.001) and reached control values (P=.089). During DR-HC, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) activity measured by tetrahydrocortisol+5 alpha-tetrahydrocortisol/tetrahydrocortisone ratio was reduced compared to TID-HC (P<.05), but remained increased vs controls (P<.001). 11 beta-HSD2 activity measured by urinary free cortisone/free cortisol ratio was decreased with TID-HC vs controls (P<.01) but normalized with DR-HC (P=.358). 5 alpha- and 5 beta-reduced metabolites were decreased with DR-HC compared to TID-HC. Tetrahydrocortisol/5 alpha-tetrahydrocortisol ratio was increased during both treatments, suggesting increased 5 beta-reductase activity. Conclusions: The urinary cortisol metabolome shows striking abnormalities in patients receiving conventional TID-HC replacement therapy, with increased 11 beta-HSD1 activity that may account for the unfavorable metabolic phenotype in primary adrenal insufficiency. Its change toward normalization with DR-HC may mediate beneficial metabolic effects. The urinary cortisol metabolome may serve as a tool to assess optimal cortisol replacement therapy.

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  • 32.
    Fellström, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Wu, Ping-Hsun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Ärnlöv, Johan
    Dalarna Univ, Dept Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females2020In: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465, Vol. 40, no 2, p. 71-74Article in journal (Refereed)
    Abstract [en]

    There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1 alpha, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

  • 33.
    Feudjo Tepie, M.
    et al.
    Amgen Ltd, Uxbridge, Middx, England..
    Banefelt, J.
    Quantify Res, Stockholm, Sweden..
    Ström, O.
    Quantify Res, Stockholm, Sweden..
    Ortsater, G.
    Quantify Res, Stockholm, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Åkesson, K.
    Skane Univ Hosp, Dept Orthoped, Lund, Sweden.;Lund Univ, Clin Sci Malmo, Lund, Sweden..
    Sprafka, J. M.
    Amgen Inc, Thousand Oaks, CA 91320 USA..
    Wagman, R. B.
    Amgen Inc, Thousand Oaks, CA 91320 USA..
    Denosumab (DMAB) Freedom Extension Pseudo Control Study: A Retrospective Cohort Study Of Comorbidities In Swedish Women With Postmenopausal Osteoporosis (PMO)2016In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, p. S154-S154Article in journal (Other academic)
  • 34.
    Freyschuss, Bo
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Cars, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Sence Res AB, Uppsala, Sweden.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Johansson, Helena
    Australian Catholic Univ, Mary McKillop Inst Hlth Res, Melbourne, Vic, Australia.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr,Geriatr Med, Gothenburg, Sweden..
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Real-World Effectiveness of Anti-Resorptive Treatment in Patients With Incident Fragility Fractures: The STORM Cohort – A Swedish Retrospective Observational Study2022In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 37, no 4, p. 649-659Article in journal (Refereed)
    Abstract [en]

    Results from real-world evidence (RWE) from the largest healthcare region in Sweden show low uptake of antiresorptive (AR) treatment, but beneficial effect in those receiving treatment, especially for the composite outcome of hip fracture or death. For RWE studies, Sweden is unique, with virtually complete coverage of electronic medical records (EMRs) and both regional and national registries, in a universal publicly funded healthcare system. To our knowledge, there is no previous RWE study evaluating the efficacy of AR treatment compared to no AR treatment after fragility fracture, including data on parenteral treatments administered in hospital settings. The Stockholm Real World Management (STORM) study cohort was established in the healthcare region of Stockholm to retrospectively assess the effectiveness of AR treatment after first fragility fracture using the regional EMR system for both hospital and primary care. Between 2012 and 2018, we identified 69,577 fragility fracture episodes among 59,078 patients, men and women, 50 years and older. Of those, 21,141 patients met inclusion and exclusion criteria (eligible cohort). From these, the final matched study cohort comprised 9840 fragility fractures (cases receiving AR treatment [n = 1640] and controls not receiving AR treatment [n = 8200]). Propensity scores were estimated using logistic regression models with AR treatment as outcome and confounders as independent variables followed by analysis using Cox proportional hazard models. Real world evidence from Sweden's largest healthcare region, comprising a quarter of the Swedish population, show that only 10% of patients receive AR treatment within 1 year after a fragility fracture. Factors associated with not receiving treatment include having a diagnosis of cardiovascular disease. In those treated, AR have positive effects particularly on the composite of fracture and death (any fracture/death and hip fracture/death) in individuals matched for all major confounders.

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  • 35. Ghanei, Iman
    et al.
    Rosengren, Bjorn E.
    Hasserius, Ralph
    Nilsson, Jan-Ake
    Mellstrom, Dan
    Ohlsson, Claes
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Karlsson, Magnus K.
    The prevalence and severity of low back pain and associated symptoms in 3,009 old men2014In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 23, no 4, p. 814-820Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to evaluate the prevalence and severity of low back pain (LBP) and the influence of sciatica and neurological deficits in old men. Mister osteoporosis Sweden includes 3,014 community-dwelling men aged 69-81 years. At study start 3,009 participants answered questions on LBP, low back pain and sciatica (LBP + SCI) or low back pain and sciatica with associated neurological deficits (LBP + SCI + NEU) during the preceding 12 months. Data are presented as proportions or medians with mid-quartile ranges. Differences between groups were tested by chi(2) test and Kruskall-Wallis test. 24 % had experienced LBP without SCI, 8 % LBP + SCI and 14 % LBP + SCI + NEU. 10 % of the men with LBP, 22 % of those with LBP + SCI, and 36 % of those with LBP + SCI + NEU rated the pain as severe (p < 0.001). 23 % of the men with LBP, 31 % of those with LBP + SCI and 50 % of those with LBP + SCI + NEU reported limitation in activity of daily living (ADL) (p < 0.001). Men with only LBP had to restrict their activities for 7 days (3-14), those with LBP + SCI 6 days (2-14) and those with LBP + SCI + NEU 10 days (3-30) (p < 0.05). The 1-year prevalence of LBP in community living men aged 69-81 years was close to 50 % but for individuals with LBP or LBP + SCI the morbidity was low with more than two-thirds having no limitations in ADL. In men with LBP + SCI + NEU more than one-third rated the pain as severe and close to half had limitations in ADL.

  • 36.
    Grassi, Lorenzo
    et al.
    Lund Univ, Dept Biomed Engn, Box 118, SE-22100 Lund, Sweden..
    Väänänen, Sami P. P.
    Kuopio Univ Hosp, Diagnost Imaging Ctr, Kuopio, Finland.;Univ Eastern Finland, Dept Appl Phys, Eastern Finland, Finland..
    Jehpsson, Lars
    Lund Univ, Dept Clin Sci Malmö, Lund, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Rosengren, Björn E.
    Lund Univ, Dept Clin Sci Malmö, Lund, Sweden..
    Karlsson, Magnus K. K.
    Lund Univ, Dept Clin Sci Malmö, Lund, Sweden..
    Isaksson, Hanna
    Lund Univ, Dept Biomed Engn, Box 118, SE-22100 Lund, Sweden..
    3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort2023In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 38, no 9, p. 1258-1267Article in journal (Refereed)
    Abstract [en]

    Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed amethod to reconstruct the 3D hip anatomy froma 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a populationbased cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120men with a hip fracture (<10 years frombaseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, Delta AUROC = 0.06) and fallers (Delta AUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach.

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  • 37.
    Harvey, N. C.
    et al.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Tremona Rd, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Tremona Rd, Southampton, Hants, England..
    Johansson, H.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden.;Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Oden, A.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden.;Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Karlsson, M. K.
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Rosengren, B. E.
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cooper, C.
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton SO16 6YD, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Tremona Rd, Southampton, Hants, England.;Univ Hosp Southampton NHS Fdn Trust, Tremona Rd, Southampton, Hants, England.;Univ Oxford, NIHR Musculoskeletal Biomed Res Unit, Oxford, England..
    McCloskey, E.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Kanis, J. A.
    Univ Sheffield, Sch Med, Ctr Metab Bone Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Ohlsson, C.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    FRAX predicts incident falls in elderly men: findings from MrOs Sweden2016In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 27, no 1, p. 267-274Article in journal (Refereed)
    Abstract [en]

    A Summary Falls and fractures share several common risk factors. Although past falls is not included as an input variable in the FRAX calculator, we demonstrate that FRAX probability predicts risk of incident falls in the MrOs Sweden cohort. Introduction Although not included in the FRAXA (R) algorithm, it is possible that increased falls risk is partly dependent on other risk factors that are incorporated into FRAX. The aim of the present study was to determine whether fracture probability generated by FRAX might also predict risk of incident falls and the extent that a falls history would add value to FRAX. Methods We studied the relationship between FRAX probabilities and risk of falls in 1836 elderly men recruited to the MrOS study, a population-based prospective cohort of men from Sweden. Baseline data included falls history, clinical risk factors, bone mineral density (BMD) at femoral neck, and calculated FRAX probabilities. Incident falls were captured during an average of 1.8 years of follow-up. An extension of Poisson regression was used to investigate the relationship between FRAX, other risk variables, and the time-to-event hazard function of falls. All associations were adjusted for age and time since baseline. Results At enrolment, 15.5 % of the men had fallen during the preceding 12 months (past falls) and 39 % experienced one or more falls during follow-up (incident falls). The risk of incident falls increased with increasing FRAX probabilities at baseline (hazard ratio (HR) per standard deviation (SD), 1.16; 95 % confidence interval (95%CI), 1.06 to 1.26). The association between incident falls and FRAX probability remained after adjustment for past falls (HR per SD, 1.12; 95%CI, 1.03 to 1.22). High compared with low baseline FRAX score (>15 vs <15 % probability of major osteoporotic fracture) was strongly predictive of increased falls risk (HR, 1.64; 95%CI, 1.36 to 1.97) and remained stable with time. Whereas past falls were a significant predictor of incident falls (HR, 2.75; 95%CI, 2.32 to 3.25), even after adjustment for FRAX, the hazard ratio decreased markedly with increasing follow-up time. Conclusions Although falls are not included as an input variable, FRAX captures a component of risk for future falls and outperforms falls history with an extended follow-up time.

  • 38.
    Harvey, N. C.
    et al.
    Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England..
    Johansson, H.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Oden, A.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Karlsson, M. K.
    Lund Univ, Skane Univ Hosp, Clin & Mol Osteoporosis Res Unit, Dept Orthoped & Clin Sci, Malmo, Sweden..
    Rosengren, B.
    Lund Univ, Skane Univ Hosp, Clin & Mol Osteoporosis Res Unit, Dept Orthoped & Clin Sci, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cooper, C.
    Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England..
    McCloskey, E. V.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Kanis, J. A.
    Univ Sheffield, Ctr Metab Bone Dis, Sheffield, S Yorkshire, England..
    Ohlsson, C.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenburg, CBAR, Sahlgrenska Acad, Gothenburg, Sweden..
    The Predictive Value Of Past Falls For Incident Falls Decreases, But That Of Frax Remains Stable, With Increasing Follow-Up Time: Findings From MROS Sweden2015In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 26, p. S143-S143Article in journal (Other academic)
  • 39.
    Harvey, N. C.
    et al.
    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Oxford, England..
    Oden, A.
    Univ Sheffield, Ctr Metab Bone Dis, Med Sch, Sheffield, S Yorkshire, England..
    Orwoll, E.
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Lapidus, J.
    Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97201 USA..
    Kwok, T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China..
    Karlsson, M.
    Lund Univ, Dept Orthopaed & Clin Sci, Skane Univ Hosp, Malmo, Sweden..
    Rosengren, B.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cooper, C.
    Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Botnar Res Ctr, Oxford, England..
    Kanis, J. A.